Our studes are primarily directed towards an understanding of the cellular response to streptococcal antigens in patients with post-streptococcal sequelae. Using blastogenesis and migration inhibition cellular assays, to date we have noted that patients with acute rheumatic fever respond primarily to streptococcal antigens present in those strains associated with rheumatic fever and not to antigens isolated from nephritis producing strains. This heightened reactivity persists for at least one year after the initial attack. Soluble extracts of these membrane antigens are also highly reactive in the test systems. An unexpected finding was the observation that many patients with acute post-streptococcal glomerulonephritis have a depressed response to streptococcal atigens during the acute phase of their disease which may persist for as long as two years after the initial attack. Cell depletion studies have demostrated that the suppressor cell population is an "adherent-cell" population. Studies are now in progress to further purify and characterize the streptococcal antigen(s) which is cross-reactive in this cellular response and to determine whether mammalian tissue antigens are also involved in the cellular response to these cross-reactive antigens.